Article
Principles of CRISPR-Cas13 mismatch intolerance enable selective silencing of point-mutated oncogenic RNA with single-base precision.
Science advances - 20 Dec 2024
Shembrey Carolyn, Yang Ray, Casan Joshua, Hu Wenxin, Chen Honglin, Singh Gurjeet J, Sadras Teresa, Prasad Krishneel, Shortt Jake, Johnstone Ricky W, Trapani Joseph A, Ekert Paul G, Fareh Mohamed
Abstract excerpt
Single-nucleotide variants (SNVs) are extremely prevalent in human cancers, although most of these remain clinically unactionable. The programmable RNA nuclease CRISPR-Cas13 has been deployed to specifically target oncogenic RNAs. However, silencing oncogenic SNVs with single-base precision remains extremely challenging due to the intrinsic mismatch tolerance of Cas13. Here, we show that introducing synthetic...
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